Dr Baljevic on Selinexor Plus Pomalidomide/Dexamethasone in R/R Myeloma

"Lower weekly dosing also facilitated median exposure time of the drug to be higher and the intensity to be higher, which is probably the reason why the long-term disease outcomes were, in fact, better. [with the 40-mg dose of selinexor vs the 60-mg dose]."

Muhamed Baljevic, MD, FACP, hematologist, medical oncologist, associate professor, medicine, Division of Hematology Oncology, director, Plasma Cell Disorders Research, director, Vanderbilt Amyloidosis Multidisciplinary Program, Vanderbilt-Ingram Cancer Center; co-chair, the Vanderbilt-Ingram Cancer Center Protocol Review and Monitoring System, discusses findings from the phase 1/1b STOMP trial (NCT02343042) evaluating the efficacy and safety of selinexor (Xpovio) in combination with pomalidomide (Pomalyst) and dexamethasone (SPd) in patients with relapsed/refractory multiple myeloma.

This trial assessed 3 selinexor dosing regimens: 40 mg once weekly (SPd-40), 60 mg once weekly (SPd-60), and 60/80 mg twice weekly (SPd-60/80). Pomalidomide was evaluated at 2 mg, 3 mg, or 4 mg once per day.

Findings presented at the 2024 ASH Annual Meeting showed that patients in the SPd-40 cohort (n = 16) achieved an overall response rate (ORR) of 43.8% (95% CI, 19.8%-70.1%) and a median progression-free survival (PFS) that was not evaluable (NE; 95% CI, 8.3-NE). The ORRs were 55.0% (95% CI, 31.5%-76.9%) and 38.9% (95% CI, 17.3%-64.3%) for the SPd-60 (n = 20) and SPd-60/80 (n = 18) cohorts, respectively. The respective median PFS in these groups were of 9.1 months (95% CI, 5.7-NE) and 10.4 months (95% CI, 2.0-NE).

Regarding safety, the most common any-grade treatment-emergent adverse effects (TEAEs) reported in the SPd-40 cohort included neutropenia (75.0%), anemia (31.%), and thrombocytopenia (25.0%). These rates were lower than those observed in the SPd-60 and SPd-60/80 BIW cohorts, where grade 3 or higher neutropenia occurred in 75.0% and 50.0% of patients, respectively. Additionally, no grade 5 adverse events were reported in the SPd-40 cohort.

Baljevic highlights that the although the ORR was higher in the SPd-60 group, patients in the SPd-40 group experienced a longer median PFS. Compared with the SPd-60 regimen, the SPd-40 regimen was also associated with a longer median treatment exposure (28.0 weeks vs 22.0 weeks) and a higher median relative dose intensity (91.3% vs 77.5%). These findings may explain why the long-term disease outcomes were improved in the SPd-40 cohort, he concludes.